A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells.

Gerhard, M; Schmees, C; Voland, P; Endres, N; Sander, M; Reindl, W; Rad, R; Oelsner, M; Decker, T; Mempel, M; Hengst, L; Prinz, C

2005

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Title:: A secreted low-molecular-weight protein from Helicobacter pylori induces cell-cycle arrest of T cells.
Document type:: Journal Article; Article
Author(s):: Gerhard, M; Schmees, C; Voland, P; Endres, N; Sander, M; Reindl, W; Rad, R; Oelsner, M; Decker, T; Mempel, M; Hengst, L; Prinz, C
Abstract:: BACKGROUND & AIMS: Although Helicobacter pylori is recognized by the human immune system, the bacteria are not eliminated and lead to a chronic inflammation of the gastric mucosa. METHODS: We investigated the interaction of H. pylori with human lymphocytes. T and B lymphocytes were isolated from H. pylori-infected patients and stimulated with anti-CD3/CD28 or interleukin-6. RESULTS: Proliferation of lymphocytes was abolished on co-incubation with different H. pylori strains (1-5 bacteria/cell) or with protein extracts of culture supernatants. Inhibition of proliferation was independent of known virulence factors. The factor is a protein or protein complex with an apparent molecular weight between 30 and 60 kilodaltons, clearly distinct from VacA. Although antigen-specific activation of T cells (as shown by nuclear factor of activated T cells [NFAT]-activation, interferon-gamma production, and CD25 or CD69 up-regulation) remained intact, cell-cycle analysis showed that S-phase entry of T cells was inhibited completely by H. pylori. Consequently, stimulated T cells arrested in the G1 phase of the cell cycle. Western blot analysis showed markedly reduced phosphorylation of the retinoblastoma protein (pRb), suggesting inhibition of G1 cyclin-dependent kinase activity. In line with this, activities of cyclin D3 and cyclin E were down-regulated, and levels of the cyclin-dependent kinase inhibitor p27Kip1 were increased. Mouse embryonic fibroblasts deficient in p27 showed a decrease in H. pylori-induced inhibition of cell proliferation, suggesting a central role for p27 in mediating H. pylori-induced G1 arrest. CONCLUSIONS: Induction of cell-cycle arrest in lymphocytes may be of major significance for the chronic persistence of bacteria in the human stomach.
Journal title abbreviation:: Gastroenterology
Year:: 2005
Journal volume:: 128
Journal issue:: 5
Pages contribution:: 1327-39
Language:: eng
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/15887115
Print-ISSN:: 0016-5085
TUM Institution:: II. Medizinische Klinik und Poliklinik (Gastroenterologie); III. Medizinische Klinik und Poliklinik (Hämatologie / Onkologie); Klinik und Poliklinik für Dermatologie und Allergologie
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